Immune system‐driven human ageing:Inflammageing

Ageing, especially human ageing can be explained by the emerging concept of para‐inflammation‐driven inflammageing, which is a coinage combining inflammation and ageing. Inflam‐mageing explains that ageing, either physiological or pathological, can be driven by a low level of a variety of pro‐inflammatory cytokines and substances produced by the innate immune system. Animals must maintain homeostasis during ageing with time against incessant attack from both intrinsic and extrinsic stimuli/antigens. These potentially harmful pro‐inflammatory signals at a variety of the later stage of life may act antagonistically to their beneficial role as developmental engines for body system formation at an earlier stage of life. The idea of inflammageing is based on an antagonistic pleiotropy theory programmed during evolution. Clinical trials including caloric restriction, sirtuin activators and p38 MAPK inhibitors against premature ageing models such as metabolic syndrome, rheumatoid arthritis and Werner syndrome have been proposed. Keywords: ageing, inflammageing, inflammation, cytokine, evolution, antagonistic pleiotropy, development, innate immunity, metabolic syndrome, rheumatoid arthritis, Werner syndrome     

肥大细胞和木犀草素参与饮食诱导肥胖及 相关并发症的研究进展

在高脂饮食诱导肥胖过程中, 大量促炎性细胞浸润到脂肪组织, 分泌促炎性因子引起慢性炎性, 导致胰岛素抵抗, 最终引起2型糖尿病和心血管疾病等慢性疾病的发生。肥大细胞作为一种重要固有免疫细胞, 参与调控了饮食诱导肥胖及上述相关疾病的发生, 而通过遗传缺失或药物稳定肥大细胞, 可以改善小鼠中高脂饮食诱导的肥胖和胰岛素抵抗。因此, 肥大细胞是潜在的治疗肥胖及相关代谢疾病的重要靶点。天然黄酮类化合物木犀草素, 是一种高效的肥大细胞稳定剂, 通过饮食添加木犀草素可以抑制高脂饮食诱导小鼠体重的增加和胰岛素抵抗的形成。本文综述了肥胖相关的免疫调控、肥大细胞在饮食诱导肥胖中的作用和木犀草素等天然肥大细胞稳定剂改善肥胖及其相关代谢疾病等方面的研究进展。     

Protective Effects of Anthocyanins in Obesity‐Associated Inflammation and Changes in Gut Microbiome

Obesity is a complex disease and a major public health epidemic. Chronic, low‐grade inflammation is a common underlying feature of obesity and associated metabolic diseases; adipose tissue is a major contributor to this systemic inflammation. Evidence shows that obesity‐associated inflammation may originate from gut dysfunction, including changes in intestinal bacteria or microbiome profiles. Increasingly, food and plant bioactive compounds with antioxidant and anti‐inflammatory properties are proposed to ameliorate obesity‐associated inflammation. Among these, the health‐promoting effects of anthocyanin‐rich foods are of interest here. Specifically, this review summarizes the reported benefits of anthocyanins in obesity‐associated inflammation and underlying molecular mechanisms, including the role of gut microbiome and cell signaling pathways regulated by anthocyanins both in vivo and in vitro.     

Role of taurine in the pathogenesis of obesity

Taurine is a sulfur‐containing amino acid that is present in mammalian tissues in millimolar concentrations. Taurine is involved in a diverse array of biological and physiological functions, including bile salt conjugation, osmoregulation, membrane stabilization, calcium modulation, anti‐oxidation, and immunomodulation. The prevalence of obesity and being overweight continues to rise worldwide at an alarming rate. Obesity is associated with a higher risk of metabolic and cardiovascular diseases, cancer, and other clinical conditions. Ingestion of taurine has been shown to alleviate metabolic diseases such as hyperlipidemia, diabetes, hypertension, and obesity in animal models. A global epidemiological survey showed that 24‐h urinary taurine excretion, as a marker of dietary taurine intake, was inversely associated with BMI, blood pressure, and plasma cholesterol in humans. In addition, taurine chloramine, an endogenous product derived from activated neutrophils, has been reported to suppress obesity‐induced oxidative stress and inflammation in adipocytes. Synthetic activity and concentration of taurine in adipose tissues and plasma have been shown to decrease in humans and animals during the development of obesity, suggesting a relationship between taurine deficiency and obesity. In this review, I summarize the effects of taurine on the progression of obesity in animal models and humans. Furthermore, I discuss possible mechanisms underlying the antiobesity effects of taurine.     

药食两用植物改善饮食诱导代谢性炎症研究进展

代谢性炎症具有缓慢性、隐匿性、持续性、关联性等特点,未加及时防治可能破坏机体稳态,导致代谢紊乱并且干扰能量平衡,继而引发肥胖、代谢综合征、代谢相关脂肪性肝病、动脉粥样硬化、2型糖尿病等难治病症。伴随着人类生活方式和饮食结构的改变,肥胖等慢性代谢性疾病已成为世界公共卫生健康备受关注的焦点,代谢性炎症作为这些疾病发病机制的启动因素,通过阻断其发生发展已成为代谢性疾病的重要防治策略。目前研究发现多种药食两用植物表现出良好的抗炎作用,其具有安全、稳定、易接受、毒副作用小及无耐药性等优势。本文通过从药食两用植物目录中筛选发挥缓解炎症、调节代谢等作用的植物及其有效成分,归纳总结改善饮食诱导代谢性疾病的相关作用机制,以期为深入研究代谢性疾病的预防和治疗提供参考。     

Diet Effects in Gut Microbiome and Obesity

The 100 trillion microbes in human gut coevolve with the host and exert significant influences on human health. The gut microbial composition presents dynamic changes correlated with various factors including host genotypes, age, and external environment. Effective manipulation of the gut microbiota through diets (both long‐term and short‐term diet patterns), probiotics and/or prebiotics, and antibiotics has been proved being potential to prevent from metabolic disorders such as obesity in many studies. The dietary regulation exerts influences on microbial metabolism and host immune functions through several pathways, of which may include selectively bacterial fermentation of nutrients, lower intestinal barrier function, overexpression of genes associated with disorders, and disruptions to both innate and adaptive immunity. Discoveries in the interrelationship between diet, intestinal microbiome, and body immune system provide us novel perceptions to the specific action mechanisms and will promote the development of therapeutic approaches for obesity.     

Arginine and nitric oxide synthase: Regulatory mechanisms and cardiovascular aspects

l ‐Arginine (l ‐Arg) is a conditionally essential amino acid in the human diet. The most common dietary sources of l ‐Arg are meat, poultry and fish. l ‐Arg is the precursor for the synthesis of nitric oxide (NO); a key signaling molecule via NO synthase (NOS). Endogenous NOS inhibitors such as asymmetric‐dimethyl‐l ‐Arg inhibit NO synthesis in vivo by competing with l ‐Arg at the active site of NOS. In addition, NOS possesses the ability to be “uncoupled” to produce superoxide anion instead of NO. Reduced NO bioavailability may play an essential role in cardiovascular pathologies and metabolic diseases. l ‐Arg deficiency syndromes in humans involve endothelial inflammation and immune dysfunctions. Exogenous administration of l ‐Arg restores NO bioavailability, but it has not been possible to demonstrate, that l ‐Arg supplementation improved endothelial function in cardiovascular disease such as heart failure or hypertension. l ‐Arg supplementation may be a novel therapy for obesity and metabolic syndrome. The utility of l ‐Arg supplementation in the treatment of l ‐Arg deficiency syndromes remains to be established. Clinical trials need to continue to determine the optimal concentrations and combinations of l ‐Arg, with other protective compounds such as tetrahydrobiopterin (BH₄), and antioxidants to combat oxidative stress that drives down NO production in humans.     

Saffron: a promising natural medicine in the treatment of metabolic syndrome

Metabolic syndrome is a disorder which encompasses obesity, high blood glucose, high cholesterol levels and high blood pressure. Moreover, metabolic syndrome is considered as the most important risk factor for cardiovascular disease (CVD). CVD is the leading cause of mortality in the world for both men and women. Several chemical drugs are available to treat metabolic risk factors, but because of the safety, efficacy, cultural acceptability and lesser side effects, nowadays herbal therapy has a critical role in the treatment of these CVD risk factors. Crocus sativus L. (saffron) is a perennial herb that belongs to the Iridaceae family. Saffron is an extensively used food additive for its colour and taste and has been widely used in traditional as well as modern medicine to treat several illnesses including cardiovascular diseases. Most of the unique properties of this plant are attributed to the presence of three major components, including crocin, safranal and crocetin. It has been proved that saffron has an important role in the management of metabolic syndrome because of its marvelous activities including anti‐diabetic, anti‐obesity, hypotensive and hypolipidaemic properties. In this review article, we discuss the beneficial properties of saffron and its active components to treat different components of metabolic syndrome and most relevant animal and human studies regarding the use of this plant in cardiovascular disease, with focus on the metabolic risk factors. This review also suggests that after randomised clinical trials, saffron may be implicated as a preventive or therapeutic agent against metabolic syndrome. © 2016 Society of Chemical Industry     

Inflammatory Diseases and Vitamin E—What Do We Know and Where Do We Go?

Inflammation‐driven diseases and related comorbidities, such as the metabolic syndrome, obesity, fatty liver disease, and cardiovascular diseases cause significant global burden. There is a growing body of evidence that nutrients alter inflammatory responses and can therefore make a decisive contribution to the treatment of these diseases. Recently, the inflammasome, a cytosolic multiprotein complex, has been identified as a key player in inflammation and the development of various inflammation‐mediated disorders, with nucleotide‐binding domain and leucine‐rich repeat pyrin domain (NLRP) 3 being the inflammasome of interest. Here an overview about the cellular signaling pathways underlying nuclear factor “kappa‐light‐chain‐enhancer” of activated B‐cells (NF‐κB)‐ and NLRP3‐mediated inflammatory processes, and the pathogenesis of the inflammatory diseases atherosclerosis and non‐alcoholic fatty liver disease (NAFLD) is provided; next, the current state of knowledge for drug‐based and dietary‐based interventions for treating cardiovascular diseases and NAFLD is discussed. To date, one of the most important antioxidants in the human diet is vitamin E. Various in vitro and in vivo studies suggest that the different forms of vitamin E and also their derivatives have anti‐inflammatory activity. Recent publications suggest that vitamin E—and possibly metabolites of vitamin E—are a promising therapeutic approach for treating inflammatory diseases such as NAFLD.     

Chemoprevention of nonalcoholic fatty liver disease by dietary natural compounds

Nonalcoholic fatty liver disease (NAFLD) refers to a wide spectrum of liver disease that is not from excess alcohol consumption, but is often associated with obesity, type 2 diabetes, and metabolic syndrome. NAFLD pathogenesis is complicated and involves oxidative stress, lipotoxicity, mitochondrial damage, insulin resistance, inflammation, and excessive dietary fat intake, which increase hepatic lipid influx and de novo lipogenesis and impair insulin signaling, thus promoting hepatic triglyceride accumulation and ultimately NAFLD. Overproduction of proinflammatory adipokines from adipose tissue also affects hepatic metabolic function. Current NAFLD therapies are limited; thus, much attention has been focused on identification of potential dietary substances from fruits, vegetables, and edible plants to provide a new strategy for NAFLD treatment. Dietary natural compounds, such as carotenoids, omega‐3‐PUFAs, flavonoids, isothiocyanates, terpenoids, curcumin, and resveratrol, act through a variety of mechanisms to prevent and improve NAFLD. Here, we summarize and briefly discuss the currently known targets and signaling pathways as well as the role of dietary natural compounds that interfere with NAFLD pathogenesis.     

Vitamin d and metabolic syndrome risk factors: evidence and mechanisms

The metabolic syndrome develops in an individual with any three of the following risk factors: obesity, diabetes, inflammation, hypertension, dyslipidemia, and thrombosis. Recent evidence suggests that vitamin D may play a role in the development of some of these risk factors. The metabolic syndrome is more common in western societies than the underdeveloped countries. Individuals in western societies usually consume a high calorie diet that lacks essential nutrients and, by virtue of being located in the northern hemisphere, they have limited sun exposures which restrict their vitamin D synthesis. Moreover, the lifestyle of these societies is considered sedentary. These dietary and environmental factors coupled with the sedentary lifestyle predispose them to metabolic syndrome risk factors. Active research revealed the role of vitamin D in the development of obesity, diabetes, inflammation, and hypertension. On the other hand, limited research has been done on the role of vitamin D in other risk factors such as dyslipidemia and thrombosis. The scientific community proposes to increase the current vitamin D fortification level in foods to reduce the risk factors of the metabolic syndrome.     

Obesity and neurological disorders: Dietary perspective of a global menace

Obesity is considered a major public health concern throughout the world among children, adolescents, as well as adults and several therapeutic, preventive and dietary interventions are available. In addition to life style changes and medical interventions, significant milestones have been achieved in the past decades in the development of several functional foods and dietary regimens to reduce this menace. Being a multifactorial phenomenon and related to increased fat mass that adversely affects health, obesity has been associated with the development of several other co-morbidities. A great body of research and strong scientific evidence identifies obesity as an important risk factor for onset and progression of several neurological disorders. Obesity induced dyslipidaemia, metabolic dysfunction, and inflammation are attributable to the development of a variety of effects on central nervous system (CNS). Evidence suggests that neurological diseases such as Parkinson's disease and Alzheimer's disease could be initiated by various metabolic changes, related to CNS damage, caused by obesity. These metabolic changes could alter the synaptic plasticity of the neurons and lead to neural death, affecting the normal physiology of CNS. Dietary intervention in combination with exercise can affect the molecular events involved in energy metabolism and synaptic plasticity and are considered effective non-invasive strategy to counteract cognitive and neurological disorders. The present review gives an overview of the obesity and related neurological disorders and the possible dietary interventions.     

左旋肉碱改善代谢综合征的作用及机制研究进展

代谢综合征是一组以肥胖、血脂异常、高血压、高尿酸血症、高血糖以及胰岛素抵抗等为主要特征的临床综合征,是心血管疾病和糖尿病的重要危险因素。研究表明,左旋肉碱,即L-肉碱,对代谢综合征具有潜在改善作用。本文对人体L-肉碱的来源及L-肉碱改善代谢综合征主要组分,如肥胖、血脂异常等的作用及机制进行综述,并讨论了L-肉碱作为氧化三甲胺前体物质的潜在健康风险问题,为代谢综合征的防治及L-肉碱的合理摄食补充及应用提供理论依据及参考。     

β‐1,3/1,6‐Glucans and Immunity: State of the Art and Future Directions

The innate immune system responds in a rapid and non‐specific manner against immunologic threats; inflammation is part of this response. This is followed by a slower but targeted and specific response termed the adaptive or acquired immune response. There is emerging evidence that dietary components, including yeast‐derived β‐glucans, can aid host defense against pathogens by modulating inflammatory and antimicrobial activity of neutrophils and macrophages. Innate immune training refers to a newly recognized phenomenon wherein compounds may “train” innate immune cells, such that monocyte and macrophage precursor biology is altered to mount a more effective immunological response. Although various human studies have been carried out, much uncertainty still exists and further studies are required to fully elucidate the relationship between β‐glucan supplementation and human immune function. This review offers an up‐to‐date report on yeast‐derived β‐glucans as immunomodulators, including a brief overview of the current paradigm regarding the interaction of β‐glucans with the immune system. The recent pre‐clinical work that has partly decrypted mode of action and the newest evidence from human trials are also reviewed. According to pre‐clinical studies, β‐1,3/1,6‐glucan derived from baker's yeast may offer increased immuno‐surveillance, although the human evidence is weaker than that gained from pre‐clinical studies.     

基于肠道菌群的黄酮类化合物生理功能研究进展

黄酮类化合物是一类具有2-苯基色原酮结构的多酚化合物,广泛存在于水果、蔬菜、茶叶中,具有抗氧化、降血脂、调节血糖和抑制炎症等功效.大量研究证实黄酮类化合物在体内的代谢吸收和生理功能的发挥与肠道菌群密切相关.本文从肠道菌群的结构和功能,参与代谢的微生物种类及产物,代谢酶的种类和活性等方面阐述黄酮化合物与肠道菌群间的相互作...     

Addressing the gut microbiome and implications for obesity

Identification of the gut microbiota as an environmental factor that modulates obesity and metabolic diseases has provided the medical and functional food industry with new targets to treat metabolic diseases. However, only limited knowledge about the mechanisms by which the gut microbiota contributes to these lifestyle diseases are known. The gut microbiota is involved in energy harvest from the diet, modulation of endocrine signalling, and promoting metabolic inflammation. This review will discuss how the gut microbiota is altered in obesity, some of the mechanisms by which it promotes disease development, and how pre- and probiotics may be used to improve metabolic diseases.     

Effects of Long‐Chain and Medium‐Chain Fatty Acids on Apoptosis and Oxidative Stress in Human Liver Cells with Steatosis

Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity‐related metabolic complications, which caused by excess energy intake and physical inactivity apart from genetic defects. The mechanisms that promote disease progression from NAFLD to further liver injury are still unclear. We hypothesize that the progression involved “2nd hit” is strongly influenced by the type of fatty acids in diets. Flow cytometric analysis showed that medium‐chain fatty acid (MCFA) markedly decreased the percentage of late apoptotic and necrotic cells compared with long‐chain fatty acid (LCFA), and MCFA inhibited the activities of caspase‐3 and ‐9 in human liver cells with steatosis. Western blot analysis found that the levels of inflammatory markers (interleukin [IL]‐6, IL‐1‐β, and tumor necrosis factor‐α) were substantially reduced by MCFA compared with LCFA. Proteomic analysis further showed that LCFA inhibited the expression of antioxidant enzymes, and increased the expression of proteins associated with oxidative stress. It was found that LCFA (palmitate), not MCFA induced apoptosis, oxidative stress and chronic inflammatory responses in the hepatic cells with steatosis. In conclusion, reasonable selection of dietary fats has potential to translate therapeutically by ameliorating disease progression in patients with NAFLD.     

Maternal late-gestation metabolic stress is associated with changes in immune and metabolic responses of dairy calves

Metabolic stress in periparturient dairy cows is characterized by excessive lipid mobilization, inflammation, and oxidative stress that is associated with immune dysfunction. Thus, metabolic stress around the time calving is linked to the development of various early-lactation health disorders. Maternal status during late pregnancy can have carryover effects on several health and production variables of neonatal calves. However, the effects of metabolic stress during gestation on metabolic and immune responses of newborn calves remain unknown. Thus, we aimed to investigate whether metabolic stress in late-gestation dairy cows is associated with changes in the metabolic and immune responses of their offspring during the first month of life. Holstein-Friesian cows (n = 12) were blood sampled at 28 and 15 d before expected calving. The average between these 2 sampling points in the serum concentrations of nonesterified fatty acids (NEFA), haptoglobin (Hp), and oxidant status index (OSi)—defined as the ratio between reactive oxygen and nitrogen species and total antioxidant potential—were calculated as indicators of the degree of lipid mobilization, inflammation, and oxidant status (OS), respectively. Calves were subsequently divided into groups (n = 6 each) according to their dams' high or low degree of lipid mobilization, inflammation, and OS. The metabolic responses of calves in each of these groups were compared weekly throughout their first month of life by assessing serum concentration of NEFA, Hp, and OSi. Additionally, whole blood was obtained from calves at each sampling period and subjected to a lipopolysaccharide (LPS)-stimulated tumor necrosis factor-α (TNF-α) production assay to assess cell-mediated innate immunity against induced inflammatory responses, using high (5 μg/mL of blood) and low (10 ng/mL) concentrations of LPS. Calves born to cows with higher NEFA or OSi showed lower body weight at birth and throughout the study, whereas no association between any of the maternal groups and average daily gain at 4 wk of age was identified. Serum concentrations of reactive oxygen and nitrogen species were higher in calves exposed to higher maternal NEFA concentrations or OSi when compared with calves born to cows with lower values of these biomarkers. Calves exposed to high maternal OS also had higher circulating concentrations of Hp and TNF-α, indicating greater basal inflammatory responses when compared with calves born to cows with a lower OSi. In contrast, LPS-induced inflammatory responses were less robust in calves exposed to higher maternal biomarkers of inflammation or OS, suggesting compromised immune responses to microbial agonists. Collectively, these data suggest that prenatal exposure to maternal parameters of metabolic stress may adversely affect some metabolic and inflammatory responses of the offspring that could influence disease susceptibility.